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. 2021 Dec;26(4):444-448.
doi: 10.1111/jns.12473. Epub 2021 Oct 29.

HINT1-related neuropathy in Greek patients with Charcot-Marie-Tooth disease

Zoi Kontogeorgiou  1 , Charalampos Voudommatis  1 , Chrisoula Kartanou  1 , Dionysis Pandis  2 , Marianthi Breza  1 , Thomas Zambelis  2 , Leonidas Stefanis  3 , Marios Panas  1 , Georgios Koutsis  1 , Georgia Karadima  1
Affiliations

HINT1-related neuropathy in Greek patients with Charcot-Marie-Tooth disease

Zoi Kontogeorgiou et al. J Peripher Nerv Syst. 2021 Dec.

Abstract

Autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) is a rare hereditary neuropathy within the Charcot-Marie-Tooth disease (CMT) spectrum, linked to mutations in the histidine triad nucleotide-binding protein 1 (HINT1) gene. HINT1-related neuropathy is particularly common in selected populations from Central and Eastern Europe but rare in Western European cohorts. It has not been investigated to date in the Greek population. We presently investigated the frequency of HINT1-neuropathy in a selected cohort of 42 Greek index patients with autosomal recessive or sporadic axonal hereditary neuropathy according to standard molecular genetics procedures. We identified 4 patients with biallelic mutations in HINT1, comprising 9.5% of all cases and 44.4% of cases also displaying neuromyotonia. The c.110G> C (p.Arg37Pro) HINT1 mutation was present in all cases (2 homozygous) and the c.250T> C (p.Cys84Arg) in 2 cases (compound heterozygous). HINT1-related neuropathy patients were characterized by early onset and neuromyotonia. Two patients had noteworthy clinical features, one case developing myoclonic epilepsy and the other displaying "adducted thumbs." We conclude that HINT1-related neuropathy is common in selected Greek patients with hereditary neuropathy within the CMT spectrum, in accordance with some, but not all, European populations.

Keywords: ARAN-NM; CMT; HINT1; dHMN; neuromyotonia.

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References

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